Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury.
J Immunol
; 187(5): 2626-31, 2011 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-21784973
ABSTRACT
We previously reported that extracellular histones are major mediators of death in sepsis. Infusion of extracellular histones leads to increased cytokine levels. Histones activate TLR2 and TLR4 in a process that is enhanced by binding to DNA. Activation of TLR4 is responsible for the histone-dependent increase in cytokine levels. To study the impact of histone release on pathology we used two models a Con A-triggered activation of T cells to mimic sterile inflammation, and acetaminophen to model drug-induced tissue toxicity. Histones were released in both models and anti-histone Abs were protective. TLR2- or TLR4-null mice were also protected. These studies imply that histone release contributes to death in inflammatory injury and in chemical-induced cellular injury, both of which are mediated in part through the TLRs.
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Base de dados:
MEDLINE
Assunto principal:
Histonas
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Síndrome de Resposta Inflamatória Sistêmica
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Receptor 2 Toll-Like
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Receptor 4 Toll-Like
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Fígado
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article